The primary requisite of programs designed to improve treatment modalities in malignant brain tumor is that an adequate number of patients be available to performs prospective randomly organized trials. Only by such trials can effective improvements in therapy be substantiated. The history of the treatment of this disease includes a number of instances in which the promise of an effective advance in treatment held out in a Phase II trial has failed to materialize in a Phase III trial. It is likely that the major reason for this failure is that an inadequate number of patients was entered. Brain Tumor Study Group data indicate that there are multiple disease characteristics which influence survival and that these prognostic variables differ from one patient to another. Thus, enough patients must be entered into a trial to distinguish between the effects of therapy and those produced by prognostic variables. Furthermore we believe that randomized prospective trials that include a control group are better than those using historical controls. The major reason for this is the occurrence during the course of trials of a change in the ability to diagnose the disease. For example, the computerized tomographic scanner (CT) produced a quantum change in the ability to diagnose brain tumor in some patients. How could it be shown that the improvement in survival that occurred over the years that the CT scan came into use was not merely a function of earlier diagnosis. Because the BTSG has always included a "control" arm consisting of surgery, radiation therapy and BCNU, we could show that despite the introduction of the CT scan the combination of surgery, radiation therapy and BCNU produced essentially the same overall effect.